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101.
Isacchi B Arrigucci S la Marca G Bergonzi MC Vannucchi MG Novelli A Bilia AR 《Journal of liposome research》2011,21(3):237-244
Artemisinin (qinghaosu), a unique endoperoxide sesquiterpene lactone isolated from Artemisia annua L., is a very active antimalarial drug, including severe and cerebral malaria. However, its therapeutical efficacy is limited due to its scarce bioavailability. In this article, artemisinin-loaded conventional and polyethylene glycol (PEGylated) liposomes were proposed as carriers to increase biopharmaceutical properties of the drug. Encapsulation efficacy was determined by high-performance liquid chromatography/diode array detection/electrospray ionization-mass spectrometry, dimensional analysis was performed by dynamic light scattering, and morphology was performed by trasmission electron microscopy. After dialysis, both liposomal formulations showed an encapsulation efficacy of more than 70%; mean diameter of all the artemisinin-loaded vesicles was approximately 130-140?nm. The polydispersity index of the formulations ranged from 0.2 to 0.3 and resulted as suitable for intraperitoneal (i.p.) administration. Pharmacokinetic profile and the main pharmacokinetic parameters of the carriers were evaluated in healthy mice i.p. Free artemisinin was rapidly cleared from plasma and hardly detected 1 hour after administration. Conversely, both liposomal formulations showed much longer blood-circulation time than free artemisinin; artemisinin was still detectable after 3 and 24 hours of administration, respectively, for conventional and PEGylated liposomes. AUC(0-24 h) values were increased by approximately 6 times in both of the liposomal formulations, in comparison with free artemisinin. A strong effect of formulation on the half-life of artemisinin was enhanced by more than 5-fold by the incorporation of PEG into liposomes. Liposomes loaded with artemisinin, especially the long-circulating vesicles, could really represent a new strategy for developing smart, well-tolerated, and efficacious therapeutic nanocarriers to treat tumors, but could also be very useful to treat parasitic disease. 相似文献
102.
Yi-Shiuan Lin Arthur Y Shaw Shi-Gang Wang Chia-Chen Hsu I-Wen Teng Min-Jen Tseng Tim HM Huang Ching-Shih Chen Yu-Wei Leu Shu-Huei Hsiao 《Journal of biomedical science》2011,18(1):1-8
Background
The extracellular calcium-sensing receptor (CaSR) belongs to family C of the G protein coupled receptors. Whether the CaSR is expressed in the pulmonary artery (PA) is unknown.Methods
The expression and distribution of CaSR were detected by RT-PCR, Western blotting and immunofluorescence. PA tension was detected by the pulmonary arterial ring technique, and the intracellular calcium concentration ([Ca2+]i) was detected by a laser-scanning confocal microscope.Results
The expressions of CaSR mRNA and protein were found in both rat pulmonary artery smooth muscle cells (PASMCs) and PAs. Increased levels of [Ca2+]o (extracellular calcium concentration) or Gd3+ (an agonist of CaSR) induced an increase of [Ca2+]i and PAs constriction in a concentration-dependent manner. In addition, the above-mentioned effects of Ca2+ and Gd3+ were inhibited by U73122 (specific inhibitor of PLC), 2-APB (specific antagonist of IP3 receptor), and thapsigargin (blocker of sarcoplasmic reticulum calcium ATPase).Conclusions
CaSR is expressed in rat PASMCs, and is involved in regulation of PA tension by increasing [Ca2+]i through G-PLC-IP3 pathway. 相似文献103.
Bernini P Bertini I Calabrò A la Marca G Lami G Luchinat C Renzi D Tenori L 《Journal of proteome research》2011,10(2):714-721
Celiac disease (CD) is an autoimmune disorder caused by a permanent sensitivity to gluten in genetically susceptible individuals. Accurate diagnosis of CD at an early stage and its treatment with a gluten-free diet (GFD) are important for optimum treatment and prognosis. Recently, by employing a noninvasive metabonomic approach, we have shown that CD has a well-defined metabonomic signature. Here we address potential CD patients, defined as subjects who do not have, and have never had, a jejunal biopsy consistent with clear CD, and yet have immunological abnormalities similar to those found in celiac patients. Sixty-one overt CD patients at diagnosis, 29 patients with potential CD, and 51 control subjects were examined by (1)H NMR of their serum and urine: out of 29 potential CD patients, 24 were classified as CD and 5 as control subjects. Potential CD largely shares the metabonomic signature of overt CD. Most metabolites found to be significantly different between control and CD subjects were also altered in potential CD. Our results demonstrate that metabolic alterations may precede the development of small intestinal villous atrophy and provide a further rationale for early institution of GFD in patients with potential CD, as recently suggested by prospective clinical studies. 相似文献
104.
MHC II in Dendritic Cells is Targeted to Lysosomes or T Cell-Induced Exosomes Via Distinct Multivesicular Body Pathways 总被引:1,自引:0,他引:1
Sonja I. Buschow Esther N. M. Nolte-'t Hoen Guillaume van Niel Maaike S. Pols Toine ten Broeke Marjolein Lauwen Ferry Ossendorp Cornelis J. M. Melief Graça Raposo Richard Wubbolts Marca H. M. Wauben Willem Stoorvogel 《Traffic (Copenhagen, Denmark)》2009,10(10):1528-1542
Dendritic cells (DCs) express major histocompatibility complex class II (MHC II) to present peptide antigens to T cells. In immature DCs, which bear low cell surface levels of MHC II, peptide-loaded MHC II is ubiquitinated. Ubiquitination drives the endocytosis and sorting of MHC II to the luminal vesicles of multivesicular bodies (MVBs) for lysosomal degradation. Ubiquitination of MHC II is abrogated in activated DCs, resulting in an increased cell surface expression. We here provide evidence for an alternative MVB sorting mechanism for MHC II in antigen-loaded DCs, which is triggered by cognately interacting antigen-specific CD4+ T cells. At these conditions, DCs generate MVBs with MHC II and CD9 carrying luminal vesicles that are secreted as exosomes and transferred to the interacting T cells. Sorting of MHC II into exosomes was, in contrast to lysosomal targeting, independent of MHC II ubiquitination but rather correlated with its incorporation into CD9 containing detergent-resistant membranes. Together, these data indicate two distinct MVB pathways: one for lysosomal targeting and the other for exosome secretion. 相似文献
105.
Background
Assessments of stair climbing in real-life situations using an optical tracking system are lacking, as it is difficult to adapt the system for use in and around full flights of stairs. Alternatively, a portable system that consists of inertial measurement units (IMUs) can be used to collect anatomical joint angles during stair ascent. The purpose of this study was to compare the anatomical joint angles obtained by IMUs to those calculated from position data of an optical tracking device.Methods
Anatomical joint angles of the thigh, knee and ankle, obtained using IMUs and an optical tracking device, were compared for fourteen healthy subjects. Joint kinematics obtained with the two measurement devices were evaluated by calculating the root mean square error (RMSE) and by calculating a two-tailed Pearson product-moment correlation coefficient (r) between the two signals.Results
Strong mean correlations (range 0.93 to 0.99) were found for the angles between the two measurement devices, as well as an average root mean square error (RMSE) of 4 degrees over all the joint angles, showing that the IMUs are a satisfactory system for measuring anatomical joint angles.Conclusion
These highly portable body-worn inertial sensors can be used by clinicians and researchers alike, to accurately collect data during stair climbing in complex real-life situations.106.
Janssen EM van Oosterhout AJ van Rensen AJ van Eden W Nijkamp FP Wauben MH 《Journal of immunology (Baltimore, Md. : 1950)》2000,164(2):580-588
Allergen-specific CD4+ Th2 cells play an important role in the immunological processes of allergic asthma. Previously we have shown that, by using the immunodominant epitope OVA323-339, peptide immunotherapy in a murine model of OVA induced allergic asthma, stimulated OVA-specific Th2 cells, and deteriorated airway hyperresponsiveness and eosinophilia. In the present study, we defined four modulatory peptide analogues of OVA323-339 with comparable MHC class II binding affinity. These peptide analogues were used for immunotherapy by s.c. injection in OVA-sensitized mice before OVA challenge. Compared with vehicle-treated mice, treatment with the Th2-skewing wild-type peptide and a Th2-skewing partial agonistic peptide (335N-A) dramatically increased airway eosinophilia upon OVA challenge. In contrast, treatment with a Th1-skewing peptide analogue (336E-A) resulted in a significant decrease in airway eosinophilia and OVA-specific IL-4 and IL-5 production. Our data show for the first time that a Th1-skewing peptide analogue of a dominant allergen epitope can modulate allergen-specific Th2 effector cells in an allergic response in vivo. Furthermore, these data suggest that the use of Th1-skewing peptides instead of wild-type peptide may improve peptide immunotherapy and may contribute to the development of a successful and safe immunotherapy for allergic patients. 相似文献
107.
Boot EP Koning GA Storm G Wagenaar-Hilbers JP van Eden W Everse LA Wauben MH 《Arthritis research & therapy》2005,7(3):R604-R615
T cells have an important role during the development of autoimmune diseases. In adjuvant arthritis, a model for rheumatoid
arthritis, we found that the percentage of CD4+ T cells expressing the activation marker CD134 (OX40 antigen) was elevated before disease onset. Moreover, these CD134+ T cells showed a specific proliferative response to the disease-associated epitope of mycobacterial heat shock protein 60,
indicating that this subset contains auto-aggressive T cells. We studied the usefulness of CD134 as a molecular target for
immune intervention in arthritis by using liposomes coated with a CD134-directed monoclonal antibody as a drug targeting system.
Injection of anti-CD134 liposomes subcutaneously in the hind paws of pre-arthritic rats resulted in targeting of the majority
of CD4+CD134+ T cells in the popliteal lymph nodes. Furthermore, we showed that anti-CD134 liposomes bound to activated T cells were not
internalized. However, drug delivery by these liposomes could be established by loading anti-CD134 liposomes with the dipalmitate-derivatized
cytostatic agent 5'-fluorodeoxyuridine. These liposomes specifically inhibited the proliferation of activated CD134+ T cells in vitro, and treatment with anti-CD134 liposomes containing 5'-fluorodeoxyuridine resulted in the amelioration of adjuvant arthritis.
Thus, CD134 can be used as a marker for auto-aggressive CD4+ T cells early in arthritis, and specific liposomal targeting of drugs to these cells via CD134 can be employed to downregulate
disease development. 相似文献
108.
V De Leo F Franchi S Danero M G Ricci S La Marca T M Urbani M L Pieroni N D'Antona A R Genazzani 《Bollettino della Società italiana di biologia sperimentale》1983,59(12):1883-1889
Controversial data have been published in these last years on the dopaminergic tonus of tubero infundibular (TIDA) neurons in hyperprolactinemic subjects. Some authors retain that L-Dopa (LD) stimulation test after pretreatment with Carbidopa (CD), a dopa decarboxylase inhibitor substance, may reveal the presence of a central Dopamine (DA) defect in patient with prolactinoma. To elucidate the reason of so different activity of DA central tonus in subjects with prolactinoma, the effects of Nomifensine (NOM), an indirect DA agonist, DOM, Carbidopa/L-Dopa (CD/LD) and LD, were studied in 26 prolactinoma patients, (basal Prl levels 50 to 280 ng/ml). The patients (24-39 years) were characterized by secondary amenorrhea with sella turcica enlargement at hypocicloidal polytomography. The NOM administration resulted unable to reduce Prl plasma levels in all the patients. On the basis of Prl response to CD/LD administration the patients were subdivided in two groups: group A, which showed a significant decrease of Prl plasma levels and group B, who did not show any significant change. LD test induced a significant Prl decrease in all patients with more evident response in these of group A. DOM administration induced a Prl rise in patients of group A, but failed to change significantly Prl levels in group B subjects. These results confirming the high validity of NOM inhibiting test in the diagnosis of tumoural hyperprolactinemic states, reveal contradictory responses to CD/LD, LD and DOM, with sustain the existence of 2 sub-group of Prolactinomas: with or without a maintained DA central tonus supporting the possibility of different etiopathogenetical factors in inducing a tumoural hyperprolactinemic states. 相似文献
109.
Morena Gabriele Laura Pucci Margherita La Marca Daniela Lucchesi Clara Maria Della Croce Vincenzo Longo Valter Lubrano 《Cellular & molecular biology letters》2016,21(1):10
This study focused on an extract from fermented flour from the Lady Joy variety of the common bean Phaseolus vulgaris. The extract, Lady Joy lysate (Lys LJ), is enriched in antioxidant compounds during the fermentation. We assessed it for its protective effect on endothelial cells treated with oxidized-LDL (ox-LDL). The oxidative stress was determined by measuring the contents of thiobarbituric acid-reactive substances and reactive oxygen metabolites. ICAM-1, ET-1 and IL-6 concentrations were assessed using ELISA. LOX-1 and CHOP expression were analyzed using both quantitative RT-PCR and ELISA or western blotting. Ox-LDL treatment induced significant oxidative stress, which was strongly reduced by pre-treatment with the extract. The ox-LDL exposure significantly enhanced ICAM-1, IL-6 and ET-1 levels over basal levels. Lys LJ pre-treatment exerted an inhibitory effect on ox-LDL-induced endothelial activation with ICAM-1 levels comparable to those for the untreated cells. IL-6 and ET-1 production, although reduced, was still significantly higher than for the control. Both LOX-1 and CHOP expression were upregulated after ox-LDL exposure, but this effect was significantly decreased after Lys LJ pre-treatment. Lys LJ alone did not alter the ICAM-1, IL-6 and ET-1 concentrations or CHOP expression, but it did significantly lower the LOX-1 protein level. Our data suggest that Lys LJ is an effective antioxidant that is able to inhibit the oxidation process, but that it is only marginally active against inflammation and ET-1 production in HMEC-1 exposed to ox-LDL. 相似文献
110.